There is a strong basis for investigation of the therapeutic potential of ecadotril in chronic congestive heart failure (CHF). Currently, optimal medical treatment of CHF is founded upon digitalis, diuretics, and vasodilator drugs (Packer, 1993). Ecadotril shares with diuretic drugs the potential to counteract circulatory volume overload by means of its promotion of the natriuretic and aldosterone-antagonistic properties of endogenous natriuretic peptides. Ecadotril also shares the potential of direct-and-indirect-acting vasodilators to reverse the vasoconstriction which characterizes chronic CHF and which leads to inexorable decline in cardiac pump function (Groden, 1993; Francis & Cohn, 1990). Ecadotril may also be expected to make a favorable impact upon the deleterious process of ventricular remodeling, i.e., thinning and eccentric hypertrophy (dilatation) of the renin-angiotensin-aldosterone hormonal axis. It is also possible, but not yet proven, that by modulating local ANP feedback loops and autocrine effects in the ventricular myocardium, ecadotril may protect the heart from this process of remodeling. This trial is a randomized, double blind, placebo-controlled, parallel arm, forced titration study comparing the additional of ecadotril 50 (then 100 then 200 then 300 then 400) mg BID, or placebo to a background of optimal conventional therapy. There is a 2 week run-in during which single-blind placebo will be added to background treatment with an ACE inhibitor and a diuretic; use of digitalis is optional. There is a forced titration after 2 weeks of each double-blind treatment regiment. The total duration of double-blind treatment is 10 weeks. The patients in the placebo and ecadotril groups will be compared for hemodynamic, biochemical and adverse event variables. A Phase III trial with Ecadotril is planned for the near future. This trial would enroll more than 500 patients with congestive heart failure.